Mitogenic signaling by substance P and bombesin-like neuropeptide receptors in astrocytic/glial brain tumor-derived cell lines.
Neuropeptides such as substance P (SP) and bombesin regulate many biological processes through binding to and activating their respective cell surface receptors. Recently, we reported that many astrocytic/glial-derived brain tumor cell lines express functional SP and bombesin receptors (43% and 85%, respectively). Activation of these neuropeptide receptors stimulates several signaling pathways that regulate transcription and translation leading to the induction of mitogenesis in several cell types including astrocytic brain tumor-derived cell lines. We have also shown that a number of signaling pathways are induced by SP and/or bombesin receptors in astrocytic/glial-derived brain tumor cell lines and demonstrated that inhibiting these path-ways by selective compounds such as PD 098059, tamoxifen, CGP 41251, and rapamycin blocks cell growth. In summary, mitogenic signaling by neuropeptides may play a role in brain tumor growth and/or tumor progression, and selective compounds capable of blocking mitogenic signaling have potential to be useful in the treatment of brain tumors.
Sharif
M
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Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
D000328:Adult; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001839:Bombesin / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002648:Child; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008934:Mitogens / Q000037:antagonists & inhibitors / Q000502:physiology; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000627:therapeutic use; D013373:Substance P / Q000502:physiology; D013629:Tamoxifen / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D008934:Mitogens; D018013:Receptors, Neuropeptide; D013629:Tamoxifen; D013373:Substance P; D020928:Mitogen-Activated Protein Kinases; D001839:Bombesin; D020123:Sirolimus